The proposed study will be conducted with Clostridium thermoacetium, and Clostridium formicoaceticum. These anaerobic bacteria synthesize acetate from CO2 via a pathway involving folic acid and vitamin B12 compounds. The following enzymes involved in tetrahydrofolate metabolism will be studied: formyltetrahydrofolate synthetase, methylenetetrahydrofolate dehydrogenase, and methylenetetrahydrofolate reductase. The two Clostridia contain large amounts of these enzymes. Our goal is to find the catalytic mechanism of these enzymes, their controls, and their physical structures. Methyl groups are transferred from methyltetrahydrofolate to a corrinoid-protein in the synthesis of acetate from CO2. This transfer will be studied, as well as the corrinoid-proteins. Previous studies have shown that formate dehydrogenase in the two Clostridia functions as a selenium-tungsten or selenium-molybdenum enzyme. The role of these metals in the formate dehydrogenase will be investigated. This is the first time a biochemical role for tungsten has been found. The Clostridia carry out an electron transport, probably, connected with phosphorylation. This will be investigated by studying electron transfer between electron carriers and oxidoreductases, which have been isolated from the two Clostridia.